Treatment of Polycythemia Vera With Hydroxyurea and Pipobroman: Final Results of a Randomized Trial Initiated in 1980

Purpose The overall impact of hydroxyurea (HU) or pipobroman treatments on the long-term outcome of patients with polycythemia vera (PV) has not been assessed in randomized studies. We report final analyses from the French Polycythemia Study Group (FPSG) study, which randomly assigned HU versus pipobroman as first-line therapy in 285 patients younger than age 65 years. Patients and Methods The full methodology has been described previously. FPSG results were updated with a median follow-up of 16.3 years. Statistical analysis was performed by using competing risks on the intention-to-treat population and according to main treatment received. Results Median survival was 17 years for the whole cohort, 20.3 years for the HU arm, and 15.4 years for the pipobroman arm (P = .008) and differed significantly from that in the general population. At 10, 15, and 20 years, cumulative incidence of acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) was 6.6%, 16.5%, and 24% in the HU arm and 13%, 34%, and 52% in the pipobroman arm (P = .004). Cumulative myelofibrosis incidence at 10, 15, and 20 years according to main treatment received was 15%, 24%, and 32% with HU versus 5%, 10%, and 21% with pipobroman (P = .02). Conclusion Data from this unique randomized trial comparing HU with another cytoreductive drug in PV showed that (1) survival of patients with PV treated with conventional agents differed from survival in the general population, (2) evolution to AML/MDS is the first cause of death, (3) pipobroman is leukemogenic and is unsuitable for first-line therapy, and (4) incidence of evolution to AML/MDS with HU is higher than previously reported, although consideration should be given to the natural evolution of PV.

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Long‐term outcome comparing histological grades of follicular lymphoma patients treated with immunochemotherapy as first‐line therapy: A retrospective analysis from two institutions

European Journal Of Haematology ◽

10.1111/ejh.13359 ◽

2019 ◽

Vol 104 (3) ◽

pp. 198-206

Author(s):

Santiago Mercadal ◽

Juan‐Manuel Sancho ◽

Fina Climent ◽

Gustavo Tapia ◽

Helena Pomares ◽

...

Keyword(s):

Follicular Lymphoma ◽

Retrospective Analysis ◽

First Line ◽

Term Outcome ◽

Long Term Outcome ◽

First Line Therapy ◽

Line Therapy

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Issues in current management of chronic myeloid leukemia: Importance of molecular monitoring on long term outcome

South Asian Journal of Cancer ◽

10.4103/2278-330x.105893 ◽

2013 ◽

Vol 02 (01) ◽

pp. 038-043 ◽

Cited By ~ 2

Author(s):

Hari Menon

Keyword(s):

Myeloid Leukemia ◽

Controversial Issues ◽

Molecular Monitoring ◽

First Line ◽

Timely Manner ◽

Current Management ◽

Term Outcome ◽

Long Term Outcome ◽

First Line Therapy

AbstractMonitoring of CML patients while on therapy is vitally important and ENL has come up with specific guidelines for the same. Since we are currently talking about operational cure, this review shall focus on evaluating the emerging data to optimize response. This requires attention to all outstanding controversial issues. Only careful, accurate and regular monitoring with specific attention to grey areas will help us select first line therapy, decide when to discontinue TKIs and also move to second line TKIs in a timely manner.

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Not BCL2 mutation but dominant mutation conversation contributed to acquired venetoclax resistance in acute myeloid leukemia

Biomarker Research ◽

10.1186/s40364-021-00288-7 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Xiang Zhang ◽

Jiejing Qian ◽

Huafeng Wang ◽

Yungui Wang ◽

Yi Zhang ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Underlying Mechanism ◽

Lymphocytic Leukemia ◽

First Line ◽

Dominant Mutation ◽

First Line Therapy ◽

Line Therapy ◽

Acute Myeloid

AbstractVenetoclax (VEN) plus azacitidine has become the first-line therapy for elderly patients with acute myeloid leukemia (AML), and has a complete remission (CR) plus CR with incomplete recovery of hemogram rate of ≥70%. However, the 3-year survival rate of these patients is < 40% due to relapse caused by acquired VEN resistance, and this remains the greatest obstacle for the maintenance of long-term remission in VEN-sensitive patients. The underlying mechanism of acquired VEN resistance in AML remains largely unknown. Therefore, in the current study, nine AML patients with acquired VEN resistance were retrospectively analyzed. Our results showed that the known VEN resistance-associated BCL2 mutation was not present in our cohort, indicating that, in contrast to chronic lymphocytic leukemia, this BCL2 mutation is dispensable for acquired VEN resistance in AML. Instead, we found that reconstructed existing mutations, especially dominant mutation conversion (e.g., expanded FLT3-ITD), rather than newly emerged mutations (e.g., TP53 mutation), mainly contributed to VEN resistance in AML. According to our results, the combination of precise mutational monitoring and advanced interventions with targeted therapy or chemotherapy are potential strategies to prevent and even overcome acquired VEN resistance in AML.

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Cost-Effectiveness of Pembrolizumab Plus Chemotherapy Versus Pembrolizumab Monotherapy in Metastatic Non-Squamous and Squamous NSCLC Patients With PD-L1 Expression ≥ 50%

Frontiers in Pharmacology ◽

10.3389/fphar.2021.803626 ◽

2022 ◽

Vol 12 ◽

Author(s):

Qiao Liu ◽

Zhen Zhou ◽

Xia Luo ◽

Lidan Yi ◽

Liubao Peng ◽

...

Keyword(s):

Cost Effectiveness ◽

Life Expectancy ◽

Cost Effective ◽

Base Case ◽

First Line ◽

Term Survival ◽

First Line Therapy ◽

Line Therapy ◽

Nsclc Patients

Objective To compare the cost-effectiveness of the combination of pembrolizumab and chemotherapy (Pembro+Chemo) versus pembrolizumab monotherapy (Pembro) as the first-line treatment for metastatic non-squamous and squamous non-small-cell lung cancer (NSCLC) with PD-L1expression ≥50%, respectively, from a US health care perspective.Material and Methods A comprehensive Makrov model were designed to compare the health costs and outcomes associated with first-line Pembro+Chemo and first-line Pembro over a 20-years time horizon. Health states consisted of three main states: progression-free survival (PFS), progressive disease (PD) and death, among which the PFS health state was divided into two substates: PFS while receiving first-line therapy and PFS with discontinued first-line therapy. Two scenario analyses were performed to explore satisfactory long-term survival modeling.Results In base case analysis, for non-squamous NSCLC patients, Pembro+Chemo was associated with a significantly longer life expectancy [3.24 vs 2.16 quality-adjusted life-years (QALYs)] and a substantially greater healthcare cost ($341,237 vs $159,055) compared with Pembro, resulting in an ICER of $169,335/QALY; for squamous NSCLC patients, Pembro+Chemo was associated with a slightly extended life expectancy of 0.22 QALYs and a marginal incremental cost of $3,449 compared with Pembro, resulting in an ICER of $15,613/QALY. Our results were particularly sensitive to parameters that determine QALYs. The first scenario analysis yielded lower ICERs than our base case results. The second scenario analysis founded Pembro+Chemo was dominated by Pembro.Conclusion For metastatic non-squamous NSCLC patients with PD-L1 expression ≥50%, first-line Pembro+Chemo was not cost-effective when compared with first-line Pembro. In contrast, for the squamous NSCLC patient population, our results supported the first-line Pembro+Chemo as a cost-effective treatment. Although there are multiple approaches that are used for extrapolating long-term survival, the optimal method has yet to be determined.

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Optimized first-line therapy for stage IV breast cancer brings long-term disease-free survival: a case report and biological analysis

Translational Breast Cancer Research ◽

10.21037/tbcr.2020.04.01 ◽

2020 ◽

Vol 1 ◽

pp. 7-7

Author(s):

Li Bian ◽

Fengrui Xu ◽

Tao Wang ◽

Huiqiang Zhang ◽

Yang Cao ◽

...

Keyword(s):

Breast Cancer ◽

Disease Free Survival ◽

Stage Iv ◽

First Line ◽

Free Survival ◽

First Line Therapy ◽

Line Therapy ◽

Stage Iv Breast Cancer ◽

Disease Free

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Chemotherapy-Free Initial Treatment of Advanced Indolent Lymphoma Has Durable Effect With Low Toxicity: Results From Two Nordic Lymphoma Group Trials With More Than 10 Years of Follow-Up

Journal of Clinical Oncology ◽

10.1200/jco.18.00262 ◽

2018 ◽

Vol 36 (33) ◽

pp. 3315-3323 ◽

Cited By ~ 25

Author(s):

Sandra Lockmer ◽

Bjørn Østenstad ◽

Hans Hagberg ◽

Harald Holte ◽

Ann-Sofie Johansson ◽

...

Keyword(s):

Optimal Timing ◽

Indolent Lymphoma ◽

First Line ◽

Term Outcome ◽

Cross Sectional ◽

Term Survival ◽

Long Term Outcome ◽

New Therapy

Purpose For indolent lymphoma, the optimal timing, sequence, and choice of therapeutic regimens remain a matter of debate. In two Nordic Lymphoma Group randomized trials, symptomatic or clearly progressing patients were treated first line with a rituximab-containing regimen without chemotherapy. The purpose of this study was to assess long-term survival, risk of transformation, and need of new therapies. Methods Data were collected at cross-sectional follow-up for 321 patients with indolent lymphoma (84% with follicular lymphomas [FL]) included in one of two Nordic Lymphoma Group trials (accrual 1998 to 1999 and 2002 to 2008). All patients received first-line therapy with one or two cycles of four weekly infusions of rituximab 375 mg/m2, and 148 were randomly allocated to the addition of interferon alfa-2a. Follow-up data were retrieved from initial trial databases and medical records on repeated clinical evaluations. Results At the end of follow-up, 73% of patients were alive, with a median follow-up after random assignment of 10.6 years. Among all, 36% (38% with FL) had never needed chemotherapy. For patients with FL who required new therapy within 24 months because of early disease progression, the 10-year survival rate was 59% versus 81% for those with longer remission. Interferon was not shown to improve long-term outcome. Transformation was diagnosed in 20% of all patients (2.4% per person-year) and in 18% with FL. An additional malignancy was found in 12%. Conclusion Approximately one third of patients with symptomatic indolent lymphoma (30% with FL, 23% without FL) did not need new therapy in the long term after first-line rituximab without chemotherapy. In the entire cohort, 10-year survival was excellent with no major safety issues, which suggests that chemotherapy can be delayed safely in the majority of patients.

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